Adipocyte differentiation is a process by which preadipocytes become adipocytes wherein many external stimuli such as hormones and complex gene expressions are involved. Among the external signals inducing adipocyte differentiation, insulin is the best known hormone and plays a critical role in regulation of fat metabolism. Preadipocytes begin to differentiate into adipocytes in response to stimulation by insulin. Insulin also stores energy in the form of lipids via a complex mechanism involving increased glucose absorption and triglyceride synthesis, and promotes absorption of fatty acids derived from lipoproteins circulating in the bloodstream by activating lipoprotein lipase. The various actions of insulin in adipocytes are accompanied by increased transcription of genes regulated by insulin as well as phosphorylation of specific proteins and their fast activation. As the adipocyte differentiation is induced by insulin, transcription and expression of transcription factors such as PPARγ, C/EBP family, ADD1/SREBP1 or the like are increased, and the transcription factors induce the adipocyte differentiation through by triggering transcription one another.
Adipocyte differentiation occurs in the order of confluence, hormonal induction, clonal expansion, growth arrest and terminal differentiation. First, when preadipocytes are grown to confluence, growth arrest occurs at the G0/G1 cell cycle boundary. Given appropriate stimulation and expression of C/EBPβ and C/EBPδ, one or two rounds of cell division occur, which is known as clonal expansion. Before the preadipocytes are fully differentiated through expression of PPARγ and C/EBPα, they undergo growth arrest. In the last stage, i.e. in terminal differentiation, mature adipocytes are produced following continued growth arrest. The preadipocytes, which were similar to fibroblasts in the early stage of differentiation, become round in shape (morphological rounding-up). As mRNAs of lipoprotein lipase or the like are expressed, the transcription factors C/EBPβ and δ are transiently induced. Then, PPARγ and C/EBPα are expressed to regulate the genes that actually determine the phenotype of adipocytes or activate their expression. Those genes include glycerophosphate dehydrogenase (GPDH), acetyl-CoA carboxylase (ACC), malic enzyme (ME), glucose transporter type 4 (Glut 4), insulin receptor (IR), adipocyte selective fatty acid binding protein 2 (aP2) or the like. Through this process, lipid droplets are produced in the cytoplasm. They grow and unite with time to form one or more larger droplets.
If differentiation of human adipocytes can be promoted, and thus, if formation and accumulation of the lipid droplets can be promoted, skin wrinkling and elasticity can be improved.